第12章 厌氧性细菌

*2004 data not finalized
CFR, case-fatality ratio
Average annual incidence (per million)
Generalized Involvement of bulbar and paraspinal muscles(trismus or
Cephalic
Primary infection in head, particularly ear; isolated or combined involvement of cranial nerves, particularly seventh cranial nerve; very poor prognosis
脑干
脊髓前角
• 典型的症状
– 苦笑面容、牙关紧闭 – 持续性背部痉挛（角弓反张） – 其它
Clinical Manifestations
DISEASE CLINCAL MANIFESTATIONSA
lockjaw, risus sardonicus, difficulty swallowing, irritability, opisthotonos); involvement of autonomic nervous system(sweating, hyperthermia, cardiac arrhythmias, fluctuations in blood pressure)
• In humans, this type of bacteria is most commonly found in the gastrointestinal tract. • It plays a role in conditions such as appendicitis(阑尾炎), diverticulitis(憩室炎), and perforation of the bowel(肠穿孔).
• 抵抗力
– 芽胞抵抗力很强，100℃1h
– 75~80℃ 10min仍保持活力
– 在干燥的土壤和尘埃中可存活数年
（二Leabharlann Baidu致病性与免疫性
所致疾病-破伤风
致病条件
• 伤口需形成厌氧微环境
– 伤口窄而深（如刺伤），有泥土或异物污染 – 大面积创伤、烧伤，坏死组织多，局部组织缺血 – 有需氧菌或兼性厌氧菌混合感染的伤口
（四）防治原则
• 特异性预防：注射破伤风类毒素
免疫程序：3、4、5月 2、7岁加强 军人及易受伤人群 3次 2次 1次
• 紧急预防：
–清创、防止创口厌氧微环境的形成； –注射破伤风抗毒素（tetanus antitoxin，TAT）, 剂量为1500-3000U； –同时注射破伤风类毒素。
• 特异性治疗：早期足量使用抗毒素 ,剂量为 10 万-20万U，四环素和红霉素抗菌治疗。
破伤风痉挛毒素
• 结构
– 菌体：一条多肽
– 释出菌体：轻链（A链）-S-S-重链（B链）
– B链：神经节苷脂结合的单位
– A链：毒性作用
破伤风痉挛毒素作用机制
• 与神经系统的结合 –B链识别运动神经元外胞浆膜上的受体并结合， 促使毒素进入细胞内小泡中 • 内在化作用 –小泡从外周神经末稍沿神经轴突逆行向上，到达 运动神经元细胞体，进入传入神经末稍，最终进 入中枢神经系统
1: Obligate aerobic bacteria gather at the top of the test tube in order to absorb maximal amount of oxygen. 2: Obligate anaerobic bacteria gather at the bottom to avoid oxygen. 3: Facultative bacteria gather mostly at the top, since aerobic respiration is the most beneficial one; but as lack of oxygen does not hurt them, they can be found all along the test tube. 4: Microaerophiles gather at the upper part of the test tube but not at the top. They require oxygen but at a low concentration. 5: Aerotolerant bacteria are not affected at all by oxygen, and they are evenly spread along the test tube.
Although tetanus is a disease that has a low incidence in the developed world due to high rates of immunization, during large-scale natural disasters, compounding factors like the types of injuries, lack of medical services and supplies, and the delay in treatment associated with an already low immunization rate result in an increased incidence and outbreaks of the disease that has higher mortality in an underdeveloped society. It is important for the urban physician that cares for trauma and critical patients to become familiar with the protocols for treatment and immunization of patients that have tetanus-prone wounds, as well as recognize the potential for outbreaks in the settings of major natural disasters. Finkelstein P, Teisch L, Allen CJ, Ruiz G.Tetanus: A Potential Public Health Threat in Times of Disaster. Prehosp Disaster Med. 2017 Feb 20:1-4.
Obligate (strict) anaerobes
• no oxidative phosphorylation( anaerobic respiration ) • fermentation • killed by toxic bi-products from oxygen (superoxide radicals and hydrogen peroxide). • lack certain enzymes – superoxide dismutase * O2-+2H+ H2O2 – catalase * H2O2 H20 + O2 – peroxidase * ROOR' + electron donor (2 e-) + 2H+ → ROH + R'OH
活性氧类（Reactive oxygen species,ROS），是生物有氧代谢过 程中的一种副产品，包括氧离子、过氧化物和含氧自由基等。
• Anaerobic bacteria are bacteria that do not live or grow in the presence of oxygen.
• 无侵袭力，仅在局部繁殖，其致病作用完全有赖于
病菌所产生的外毒素
致病因子
• 对氧敏感的破伤风溶血毒素(tetanolysin)
– 对氧敏感
• 质粒编码的破伤风痉挛毒素(tetanospasmin)
– 属神经毒(neurotoxin)，毒性极强(对人致死量<1µ g)
– 蛋白质，不耐热(65 ℃，30min)
Involvement of muscles in area of primary injury; infection may precede generalized disease; favorable prognosis Generalized disease in neonates; infection typically originates from umbilical stump;very poor prognosis in infants whose mothers are nonimmune
第十二章 厌氧性细菌 （anaerobic bacteria）
第一节 厌氧性芽胞杆菌 第二节 无芽胞厌氧菌
概 述
• 厌氧性细菌必须在无氧环境下才能生长繁殖。 • 根据能否形成芽胞，厌氧性细菌分为：
– 厌氧芽胞梭菌属
• 破伤风梭菌 • 产气荚膜梭菌 • 肉毒梭菌 • 艰难梭菌
– 无芽胞厌氧菌
• Obligate anaerobes will die when exposed to atmospheric levels of oxygen.
Localized Neonatal
免疫性
• 破伤风免疫属外毒素免疫，主要是抗毒素发
挥中和作用（毒素与中枢神经组织结合非常
牢固，一旦结合即非抗毒素所能中和）；
• 病后不会获得牢固免疫力；
• 获得有效抗毒素的途径是人工免疫。
（三）微生物学检查法
• 一般不进行涂片镜检和分离培养；
• 典型的症状和病史即可作出诊断。
• 致病菌产生外毒素致病，病情严重；
• 防治：类毒素与抗毒素。
一、破伤风梭菌
（C．tetani）
破伤风（tetanus）的病原菌
(一) 生物学性状
• 形态与染色
–菌体细长，有周边鞭毛，无荚膜 –芽胞正圆，位于菌体顶端，使细菌呈鼓槌状 –G+
• 培养特性和生化反应
–严格厌氧 –血平板上，有β溶血
（一）生物学性状
破伤风痉挛毒素作用机制
• 膜的转位
–通过重链N端的介导产生膜的转位使轻链进入胞质溶胶
• 胞质溶胶中作用靶的改变
–A链发挥毒性作用，使储存抑制性神经介质小泡膜蛋白发生 改变，阻止抑制性神经介质γ-氨基丁酸的释放，使肌肉活
动的兴奋与抑制失调，造成强直性痉挛
The A-chain, a zinc endopeptidase, attacks the vesicle-associated membrane protein (VAMP). This stops the affected neurons from releasing the inhibitory neurotransmitters GABA (gamma-aminobutyric acid) and glycine by degrading the protein synaptobrevin.
Endogenous versus exogenous infection
• endogenous
– normal human flora
• exogenous
– environment (e.g. soil)
第一节 厌氧芽胞梭菌属
(Clostridium)
概 述
• 严格厌氧菌，革兰染色阳性大杆菌； • 芽胞比菌体粗，菌体膨大呈梭状，抵抗力强； • 周鞭毛，无荚膜（除产气荚膜梭菌外）；
Tetanus in the United States: 1947-2004*
5 4
4.1/million
CFR 91%
1972-2001
per million
3 2 1 0
1947 1960 1970 1980 1990 2000
Incidence Mortality
2004: 32 cases = 0.11 / million CFR 13%